基质金属蛋白酶-9和金属蛋白酶组织抑制物-1在IgA肾病肾组织中的表达

目的 探讨基质金属蛋白酶－9（MMP－9）／金属蛋白酶组织抑制物－1（TIMP－1）系统在IgA肾病肾组织中的表达及其对IgA肾病的进展的影响。方法 采用免疫组织化学和原位杂交技术,分别在蛋白质和基因水平检测38例IgA肾病患者肾组织中的MMP－9和TIMP－1的变化。结果 MMP－9在正常肾脏肾小球的脏层上皮细胞和内皮细胞有少量表达,在肾小管上皮细胞和间质血管壁也有少量表达;在IgA肾病中,MMP－9在系膜增殖性肾小球和间质血管壁的表达均明显增多（P＜0．001）,而在硬化肾小球内的表达则明显减少,肾小管细胞的MMP－9表达无明显变化。TIMP－1在正常肾组织中不能检出,在IgA肾病患者具有系膜增殖性病变的肾小球中有微量表达,在增殖在很重但尚未完全硬化的肾小球内表达增多,在肾小管间质表达最为明显（P＜0．001）,其主要见于肾小管细胞、间质细胞和血管内皮细胞。肾组织中的TIMP－1表达与血清肌酐水平呈显著相关（P＜0．05）,与肾小管间质的纤维化和炎细胞浸润程度亦明显相关（P值均＜0．01）。肾小球中的MMP－9表达与尿蛋白无明显相关性,但与血清肌酐水平呈显著负相关（P＜0．05）。结论 MMP－9和TIMP－1的异常表达可能是影响IgA肾病进展的因素之一。

Expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in IgA nephropathy

Objective To explore the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the renal tissue of patients with IgA nephropathy. Methods Immunohistochemistry and in situ hybridization assays were applied to detect the expression of mRNA and protein of TIMP-1, as well as the protein expression of MMP-9 in renal tissue of 38 patients with IgA nephropathy. Results MMP-9 was normally expressed, at a low level, in the glomerular endothelial cells and visceral epithelial cells, as well as in tubular epithelial cells and walls of vessels. The expression of MMP-9 was significantly increased in mesangial proliferative glomeruli and interstitial vascular walls of IgA nephropathy patients (P<0.001), but markedly decreased in sclerotic glomeruli and not apparently altered in the tubule. No expression of TIMP-1 could be detected in normal renal tissue. TIMP-1 was only slightly expressed in the mesangioproliferative glomeruli of IgA nephropathy patients. TIMP-1 expression was increased notably in partially sclerotic glomeruli, and most prominently expressed in tubulointerstitium (P< 0.01), mainly in tubular epithelial cells, interstitial cells, and vascular endothelial cells. The expression of TIMP-1 was distinctly associated with the level of serum creatinine (P<0.05), tubulointerstitial fibrosis (P<0.01), and tubulointerstitial infiltration of leukocytes (P<0.01). MMP-9 expression did not correlate with proteinuria, but negatively correlated with serum creatinine levels (P<0.05). Conclusion The abnormal expressions of MMP-9 and TIMP-1 may contribute to the progression of IgA nephropathy.